Cis-13-PGA1 analogs

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is of the cis configuration. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 595,869, filed July 14, 1975, now issued as U.S. Pat. No. 4,026,909 on May 31, 1977.

The present invention relates to prostaglandin analogs for which the essential material constituting a disclosure therefor is incorporated by reference here from U.S. Pat. No. 4,026,909, issued May 31, 1977. 

I claim:
 1. A compound of the formula ##STR1## wherein Y is cis--CH═CH--; wherein g is 2, 3, or 4;Wherein M₁ is ##STR2## wherein R₅ and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆ is methyl only when the other is hydrogen; Wherein L₁ is ##STR3## or a mixture of ##STR4## wherein R₃ and R₄ are hydrogen, methyl, fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro; Wherein m is 1 to 5, inclusive; and Wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 2. A compound according to claim 1, wherein g is
 2. 3. A compound according to claim 2, wherein m is
 3. 4. A compound according to claim 3, wherein at least one of R₃ and R₄ is fluoro.
 5. A compound according to claim 4, wherein R₃ and R₄ are both fluoro.
 6. A compound according to claim 5, wherein R₅ and R₆ are hydrogen.
 7. 15-EPI-2,2,16,16-Tetrafluoro-cis-13-PGA₁, methyl ester, a compound according to claim
 6. 8. A compound according to claim 3, wherein at least one of R₃ and R₄ is methyl.
 9. A compound according to claim 8, wherein R₃ and R₄ are both methyl.
 10. A compound according to claim 9, wherein R₅ and R₆ are both hydrogen.
 11. 15-epi-2,2-Difluoro-16,16-dimethyl-cis-13-PGA₁, methyl ester, a compound according to claim
 10. 12. A compound according to claim 3, wherein R₃ and R₄ are both hydrogen.
 13. A compound according to claim 12, wherein R₅ and R₆ are both hydrogen.
 14. 15-epi-2,2-Difluoro-cis-13-PGA₁, methyl ester, a compound according to claim
 13. 15. A compound according to claim 12, wherein R₅ is methyl.
 16. 15-epi-2,2-Difluoro-15-methyl-cis-13-PGA₁, methyl ester, a compound according to claim
 15. 17. A compound according to claim 12, wherein R₆ is methyl.
 18. 15-epi-2,2-Difluoro-cis-13-PGA₁, 15-methyl ether, methyl ester, a compound according to claim
 17. 19. A compound of the formula ##STR5## wherein Y₁ is cis--CH═CH--; wherein g is 2, 3, or 4;wherein M₁ is ##STR6## wherein R₅ and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆ is methyl only when the other is hydrogen; wherein L₂ is ##STR7## or a mixture of ##STR8## wherein R₃ and R₄ are hydrogen or fluoro, being the same or different, with the proviso that at least one of R₃ and R₄ is fluoro; wherein m is one to 5, inclusive; and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 20. A compound according to claim 19, wherein g is
 4. 21. A compound according to claim 20, wherein m is
 3. 22. A compound according to claim 21, wherein R₃ and R₄ are both fluoro.
 23. A compound according to claim 22, wherein R₅ and R₆ are hydrogen.
 24. 15-epi-2a,2b-Dihomo-16,16-difluoro-cis-13-PGA₁, methyl ester, a compound according to claim
 23. 25. A compound according to claim 19, wherein g is
 2. 26. A compound according to claim 25, wherein m is
 3. 27. A compound according to claim 26, wherein both R₃ and R₄ are fluoro.
 28. A compound according to claim 27, wherein R₅ and R₆ are hydrogen.
 29. 15-epi-16,16-difluoro-cis-13-PGA₁, methyl ester, a compound according to claim
 28. 30. A compound of the formula ##STR9## wherein Y is cis--CH═CH--; wherein g is 2, 3, or 4;wherein M₂ is ##STR10## wherein L₃ is ##STR11## or a mixture of ##STR12## wherein R₃ and R₄ are hydrogen or methyl, being the same or different; wherein m is one to 5, inclusive; and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 31. A compound according to claim 30, wherein g is
 2. 32. A compound according to claim 31, wherein m is
 3. 33. A compound according to claim 32, wherein at least one of R₃ and R₄ is methyl.
 34. A compound according to claim 32, wherein R₃ and R₄ are both methyl.
 35. A compound according to claim 32, wherein R₃ and R₄ are hydrogen.
 36. 15-epi-cis-13-PGA₁, methyl ester, 15-methyl ether, a compound according to claim
 35. 37. A compound of the formula ##STR13## wherein Y is cis--CH═CH--; wherein M₃ is ##STR14## wherein R₅ is hydrogen or methyl; wherein L₄ is ##STR15## or a mixture of ##STR16## wherein R₃ and R₄ are hydrogen or methyl, being the same or different, with the proviso that one of R₃ and R₄ is methyl;wherein m is 1 to 5, inclusive; and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 38. A compound according to claim 37, wherein g is
 4. 39. A compound according to claim 38, wherein m is
 3. 40. A compound according to claim 39, wherein R₃ and R₄ are both methyl.
 41. A compound according to claim 40, wherein R₅ is hydrogen.
 42. 15-epi-2a,2b-Dihomo-16,16-dimethyl-cis-13-PGA₁, methyl ester, a compound according to claim
 41. 43. A compound according to claim 37, wherein g is
 2. 44. A compound according to claim 43, wherein m is
 3. 45. A compound according to claim 44, wherein R₃ and R₄ are both methyl.
 46. A compound according to claim 45, wherein R₅ is hydrogen.
 47. 15-epi-16,16-Dimethyl-cis-13-PGA₁, methyl ester, a compound according to claim
 46. 48. A compound of the formula ##STR17## or a mixture comprising that compound and the enantiomer thereof; wherein g is 2 to 4;wherein m is 1 to 5; and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 49. 15-epi-cis-13-PGA₁, methyl ester, a compound according to claim
 48. 